This project is designed to identify those regulators of collagen synthesis which are related to fibrous plaque formation in rabbit aorta. Aorta smooth muscle cells derived from normal rabbits and from rabbits with fibrous aortic plaques induced by epinephrine-thyroxine injections will be grown in tissue culture. Parameters of collagen synthesis, including the amount and type of collagen (via labeling experiments with 3H- or 14C-proline) found in cells and media, prolyl hydroxylase, UDP galactosyl and glucosyltransferase, and lysyl oxidase will be determined in relation to non-collagenous protein synthesis throughout the growth cycle of these cells. Extracts and column fractions (including lysosomal enzymes) from rabbit aorta with fibrous plaques will be added to smooth muscle cell cultures to test for the presence of activators of collagen synthesis. Parallel experiments will be conducted using blood or washed platelet fractions obtained from rabbits at various times during plaque development. Known activators of parameters of collagen synthesis will be added to cultures to determine changes in sensitivity of smooth muscle cells from aorta with fibrous plaques. Macrophages of fractions thereof obtained from wound repair systems will be added to the cells in culture to determine if these cells contain or produce substances capable of stimulating collagen synthesis.